ABSTRACT
Introduction: In Duchenne muscular dystrophy (DMD) muscle is replaced by adipose tissue. The role of dietary intake (DI) in DMD has not been evaluated. In this study we examined body ...composition, body mass index (BMI), and adequacy of DI in patients with DMD and evaluated the influence of DI on body composition. Methods: Patients (n = 101; age 3–18 years; BMI 11.8–29.5 kg/m2) completed a dietary recall to determine DI and then underwent dual‐energy X‐ray absorptiometry to determine body composition. Results: Preschool‐age and school‐age boys with DMD had high total energy intake. Protein intake per kilogram exceeded recommendations. As age increased, the percentage of boys with abnormal BMI and fat mass increased, while lean mass decreased. Dietary intake did not predict body fat or lean mass. Discussion: Age‐dependent changes in BD in boys with DMD may be due to endogenous metabolic factors related to the underlying disease process and to disease‐related mobility impairments. Muscle Nerve 59:295–302, 2019
See editorial on pages 277–279 in this issue.
Background
Omega‐3 long chain polyunsaturated fatty acids (LCPUFA) reduce circulating cytokines produced by monocytes. Nevertheless, whether the omega‐3 LCPUFA regulate the monocytes and their ...cytokines in Duchenne muscular dystrophy (DMD) is unknown. The aim of this study was to evaluate whether circulating pro‐inflammatory monocytes are increased and whether omega‐3 LCPUFA selectively suppress these monocytes and their cytokines in patients with DMD.
Methods
This was a double‐blind, randomized, placebo‐controlled pilot study carried out in patients with DMD supplemented with omega‐3 LCPUFA (n = 6) or sunflower oils (placebo, n = 6) for 6 months. Monocytes and their cytokines were measured at baseline and after 1, 2, 3, and 6 months of supplementation.
Results
The anti‐inflammatory monocytes (median, 95% CI) are increased at month 3 (−0.46 −13.5–9.5 vs. 8.4 5.5–12.5, p = 0.05) in the omega‐3 LCPUFA group compared with the placebo group. The pro‐inflammatory monocytes (−5.7 −63.8–114.1 vs. −51.9 −91.2 to −25.4, p = 0.026 and −16.4 −50.8–50.6 vs. −57.9 −86.9 to −18.5, p = 0.045 at months 3 and 6, respectively) and their cytokine interleukin 6 (−11.9 −93.5–148.9 vs. −64.7 −77.8 to −42.6, p = 0.019 at month 6) decreased in the omega‐3 LCPUFA group compared with the placebo group. Pro‐inflammatory monocytes decreased and anti‐inflammatory monocytes were augmented (p < 0.05) during the 6 months of supplementation with omega‐3 LCPUFA.
Conclusions
This pilot study suggests that supplementation with omega‐3 LCPUFA could have a selective reductive effect on pro‐inflammatory monocytes and their cytokines in patients with DMD. These findings also support the performance of studies in a significant population to explore the role of omega‐3 LCPUFA on monocyte populations and their cytokines in patients with DMD. This research was registered at clinicaltrials.gov (NCT018264229).
In Duchenne muscular dystrophy, muscle fiber is damaged, (1) resulting in a chronic inflammatory process (2), (3), (4), and (5). We propose that omega‐3 long chain polyunsaturated fatty acids (LCPUFA) are incorporated into muscle fiber (A). These fatty acids are precursors of anti‐inflammatory molecules (B) and also block the synthesis of pro‐inflammatory cytokines (C). The downregulation of these cytokines could modulate monocyte subpopulations by increasing the anti‐inflammatory monocytes, decreasing the intermediate and pro‐inflammatory monocytes (D), and regulating the cytokines produced by those cells. The modulation of monocyte subpopulations can influence the differentiation of anti‐inflammatory monocytes and favor the activation of the anti‐inflammatory cascade (E).
ABSTRACT
Introduction: Patients with Duchenne muscular dystrophy (DMD) demonstrate decreased bone mineral density (BD). It is not clear which factors exert the greatest impact on BD loss in these ...patients.
Methods: In 63 patients with DMD, serum cytokines (interleukin IL‐1, IL‐6, and tumor necrosis factor‐beta TNF‐β), C‐reactive protein (CRP), creatine kinase (CK), muscle function (by Vignos scale), body composition, and total BD (the latter 2 measured by dual‐energy X‐ray absorptiometry, or DEXA) were determined.
Results: The main factors associated with BD loss were muscle function (34.0%; β = −0.139; P < 0.023) and age (36.7%; β = −0.151; P = 0.004). Cytokines, CRP, body fat mass, and CK did not contribute to BD loss.
Discussion: Muscle function and age contribute to BD loss in DMD. We propose that a cut‐off of at least 6 points for the Vignos scale and at least 10.5 years of age predict a Z‐score of less than or equal to −2.0. Muscle Nerve 59:417–421, 2019
Objectives
This study aimed to evaluate whether the expression of circulating dystromiRs and a group of oxidative stress‐related (OS‐R) miRNAs is associated with muscle injury and circulating ...metabolic parameters in Duchenne muscular dystrophy (DMD) patients.
Methods
Twenty‐four DMD patients were included in this cross‐sectional study. Clinical scales to evaluate muscle injury (Vignos, GMFCS, Brooke, and Medical Research Council), enzymatic muscle injury parameters (CPK, ALT, and AST), anthropometry, metabolic indicators, physical activity, serum dystromiRs (miR‐1‐3p, miR‐133a‐3p, and miR‐206), and OS‐R miRNAs (miR‐21‐5p, miR‐31‐5p, miR‐128‐3p, and miR‐144‐3p) levels were measured in ambulatory and non‐ambulatory DMD patients.
Results
DystromiRs (except miR‐1‐3p) and miRNAs OS‐R levels were lower (p‐value <.05) in the non‐ambulatory group than the ambulatory group. The expression of those miRNAs correlated with Vignos scale score (For instance, rho = −0.567, p‐value <0.05 for miR‐21‐5p) and with other scales scores of muscle function and strength. CPK, AST, and ALT concentration correlated with expression of all miRNAs (For instance, rho = 0.741, p‐value <.05 between miR‐206 level and AST concentration). MiR‐21‐5p level correlated with glucose concentration (rho = −0.369, p‐value = .038), and the miR‐1‐3p level correlated with insulin concentration (rho = 0.343, p‐value = .05).
Conclusions
Non‐ambulatory DMD patients have lower circulating dystromiRs and OS‐R miRNAs levels than ambulatory DMD patients. The progressive muscle injury is associated with a decrease in the expression of those miRNAs, evidencing DMD progress. These findings add new information about the natural history of DMD.
Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether ...NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl concentrations change according to the disease severity in DMD patients. Moreover, we assessed whether OS correlated with muscle injury, clinical characteristics, physical activity, and antioxidant food consumption (AFC). A total of 28 DMD patients participated in this study. OS markers, metabolic indicators, and enzymatic markers of muscle injury were measured in circulation. Muscle injury was measured with clinical scales, and physical activity and AFC were evaluated with questionnaires. Nrf2 concentration was lower (
0.01), and malondialdehyde concentration was higher (
< 0.05) in non-ambulatory patients than in ambulatory patients. Nrf2 correlated with age (
= -0.387), Vignos scale (
= -0.328), GMFCS scale (
= -0.399), and Brooke scale scores (
= -0.371) (
< 0.05). MDA correlated with Vignos (
= 0.317) and Brooke scale scores (
= 0.414) (
≤ 0.05). In conclusion, DMD patients with the worst muscle function had more significant oxidative damage and lower antioxidant function than DMD patients with better muscle function.
Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with ...obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.
Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial ...was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group:
= 105; control-group:
= 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100;
= 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%);
= 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
Human milk microbiota is a unique bacterial community playing a relevant role in infant health, but its composition depends on different factors (woman health, lactation stage, and geographical ...lactation). However, information is lacking regarding some other factors that may affect the bacterial community of human milk. In this study we aimed to study the impact of the sample collection method and the skimming procedure using culture-dependent and culture-independent techniques to study the human milk microbial profile. One set of milk samples was provided by women (n = 10) in two consecutive days; half of the samples were collected the first day by manual expression and the other half on the second day by pumping. The rest of the participants (n = 17) provided milk samples that were fractionated by centrifugation; the bacterial profiles of whole milk and skimmed milk were compared by culture techniques in 10 milk samples, while those of whole milk, fat and skimmed milk were subjected to metataxonomic analysis in seven samples. Globally, the results obtained revealed high interindividual variability but that neither the use of single-use sterile devices to collect the sample nor the skimming procedure have a significant impact of the microbial profile of human samples.
Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid ...metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.
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